1. Field of the Invention
The present invention relates to the process for the preparation of chiral 3,4-epoxybutyric acid and the salt thereof expressed by the following formula 1, wherein (S)-3-activated hydroxybutyrolactone as a raw material and other inexpensive reactants are utilized so as to undergo an efficient ring-opening reaction and epoxydation with an inversion of chiral center. ##STR1##
2. Description of the Prior Art
Chiral 3,4-epoxybutyric acid of formula 1 or the ester compound thereof is an useful raw material for the preparation of various chiral compounds due to the synthetic utility of the epoxy group. For example, (R)4-amino-3-hydroxybutyrolactone (GABOB) prepared from (R)-3,4-epoxybutyric acid is widely known for its use as an anti-epileptic or hypotensive drug [Otsuka, M., Obata. K., Miyata, Y., Yaneka, Y., J. Neurochem. (1971) 18, 287; Buscaino, G., A., Ferrari, E., Acta Neurol. (1961) 16, 748; DeMaio, D., Madeddu, A., Faggioli, L., Acta Neurol. (1961) 16, 366; Ushinkoba, K., Nippon Seirigaku Zassni (1959) 21, 6161.
The examples for the preparation of chiral (R)-3,4-epoxybutyric acid in the prior art are as follows: In the case of the process through the oxidation reaction after stereo-selectively introducing the epoxy group via asymunetric epoxydation reaction U. Org. Chem., vol. 49, 3707.about.3711(1984)], the low yield of 11.about.25% and stereo-selectivity of 55% ee result therefrom, which is rather problematic for the industrial purpose.
Another method is selectively obtaining (R)-3,4-epoxybutyric acid ester with the target chiral center by performing a biological optical resolution on the racemic 3,4-epoxybutyric acid ester, which in turn can be obtained via chemical method [Helvetical Chimica Acta, vol. 70, 142.about.152(1987); Europe Patent 237,983(1987)]. In the case above, the stereo-selectivity is superior. However, the reaction time of approximately 24 hours is required, and the yield of more than 50% cannot be expected as is the characteristic of the biological optical resolution reaction.
On the other hand, the method of preparing (S)-3,4-epoxvbutyric acid ethyl ester from (S)-3-hydroxybutyrolactone, or preparing (R)-3,4-epoxybutvric acid ethyl ester from (R)-3-hydroxybutyrolactone is well known [Larcheveque, M., Henrot, S., Tetrahedron Letters, (1987) 28, 1781; Larcheveque, M., Henrot, S., Tetrahedron, (1990) 46, 4277]. However, iodotrimethyl silane and silver oxide are rather expensive, and difficult anhydrous condition is required therein.
The optically pure 3-hydroxybutyrolactone has seldom been utilized as a chiral raw material in the past due to the difficulty in its preparation. But, recently, the very inexpensive and facile method of preparing (S)-3-hydroxybutyrolactone through oxidation and successive cyclization from inexpensive natural D-carbohydrates and hydrogen peroxide has been developed (U.S. Pat. Nos. 5,292,939, 5,319,110, 5,374,773). As a result, (S)-3-hydroxybutyrolactone is being utilized as a pivotal raw material in the preparation of various chiral compounds, and the extent of its use will be expanded.